C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

Nat Commun. 2016 Oct 31:7:13298. doi: 10.1038/ncomms13298.

Abstract

Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a 'zipper'-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Pairing
  • Crossing Over, Genetic
  • DNA-Binding Proteins
  • Electroporation
  • Female
  • Fertility*
  • Genetic Variation
  • Genome
  • HEK293 Cells
  • Haploidy
  • Humans
  • Male
  • Meiosis
  • Mice
  • Nuclear Proteins / metabolism
  • Recombination, Genetic
  • Synaptonemal Complex / metabolism*
  • Testis / pathology
  • Transcription, Genetic
  • Two-Hybrid System Techniques

Substances

  • 4930447C04Rik protein, mouse
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SYCE1 protein, mouse
  • Sycp1 protein, mouse
  • Sycp3 protein, mouse